Sub-Visible Particle Measurement by Light Obscuration

Sub-Visible Particle Measurement by Light Obscuration

Introduction

Sub-Visible Particle Measurement to the Ph Eur 2.9.19 and USP<788> by Light Obscuration set the standards for solutions for injection or infusion which are required to be clear and practically free from particles when examined under suitable conditions of visibility.

The USP & Ph Eur set limits for the acceptable quantity of particulate matter in solutions for injection or infusion depending on the size of the container as follows in the table below:

The above limits are set for patient safety with adverse reactions concerns, e.g. mechanical obstruction with lung as target, injection site reactions, phlebitis and granuloma.

Sub-Visible Particle Measurement

Parenteral drugs are generally administered to patients by means of injections and must be essentially free of visible particles. The system requirements for a light obscuration instrument utilized to comply with Ph Eur 2.9.19 and USP<788> include a light obscuration sensor with appropriate sample feeding device, a sensor and a sampler.

The sensor must be calibrated for size at a number of points, tested for resolution, and validated for count efficiency. The concentration range should be greater than the concentration of the particles to be counted. The dynamic range must contain the smallest size particle to be quantified.

The accuracy of the sample volume must be within 5% of the appropriate sample volume for the test. For reporting, particle concentration must be greater than 10 and 25µm.

Sources of Particles

Particulate contamination can come from the solution itself and its ingredients, the production process and its variables (the environment, equipment & personnel), the products packaging and the preparation of the product for administration. These can be divided into two sources:

For the Biopharmaceutical industry protein products may contain proteinaceous particles at release, or protein particles may form during storage. Industry experience has demonstrated that therapeutic proteins such as monoclonal antibodies can exhibit a propensity for self-association, leading to the formation of aggregates that range in size from nanometres (oligomers) to microns (subvisible and visible particles). As a result, the requirement for drug product appearance for monoclonal antibodies was changed from “without visible particles” to “without visible particles unless otherwise authorised or justified”.

Source BioScience

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